Fluorinated Coumarin Derivatives as Selective PET Tracer for MAO-B Imaging

Area of Science:

• Neuroscience
• Radiochemistry
• Molecular Imaging

Background:

• Monoamine oxidase-B (MAO-B) is a key biomarker for reactive astrocytes in neuroinflammation and neurodegenerative diseases.
• MAO-B is located on the outer mitochondrial membrane of astrocytes.

Purpose of the Study:

• To synthesize novel fluorinated coumarin derivatives.
• To evaluate their structure-activity relationship and subtype selectivity for MAO-B.
• To identify a potential PET tracer for MAO-B imaging.

Main Methods:

• Synthesis of fluorinated coumarin derivatives.
• Structure-activity relationship and subtype selectivity evaluation.
• Preclinical bioevaluation using in vivo PET imaging and ex vivo autoradiography in rats.
• Inhibition studies with Selegiline.

Main Results:

• Identified a novel PET tracer, [18F]8, with high affinity for MAO-B (IC50 = 0.59 nM).
• [18F]8 demonstrated favorable brain pharmacokinetics in rats (SUVmax = 2.15 at 2 min, brain2min/60min = 7.67).
• Selegiline effectively inhibited radiolabeling in regions of MAO-B expression.

Conclusions:

• [18F]8 is a promising PET tracer candidate for MAO-B imaging.
• Further evaluation is warranted for its clinical application in neurodegenerative diseases.